The aim of this proposal is to analyze the effects of aqueous humor on cell proliferation by conjunctival fibroblasts. We hypothesize that aqueous humor contains both stimulators and inhibitors of cell growth, and that the proliferative response is modulated by the relative concentrations of these agents in the aqueous and by the proliferative state of the target tissues. We suggest that understanding the growth effects of aqueous humor will help explain why filtration surgery for glaucoma can fail. Accordingly, we propose that the maintenance of a functioning filtering fistula is dependent upon balance of growth effectors in the aqueous humor that bathes the surgical site: Excess growth stimulation may cause overgrowth and closure of the surgically--formed filtering apparatus. This application defines a sensitive, reproducible and quantifiable radioautographic assay for analysis of proliferation effects of aqueous humor. This assay will be used to analyze samples of both human and animal (rabbit) aqueous. The assay will also be used to conduct in vitro studies of some commercially-available antineoplastic drugs to determine if these could be focally delivered to retard undersirable fibroblast proliferation at the site of filtration surgery. This in vitro test is the first step toward our long term goal of devising methods to reduce the incidence of failure of glaucoma surgery. The radioautographic assay will also be used to determine if rabbit ciliary body is the source of factor(s) secreted into the aqueous that affect fibroblast growth. These studies are aimed at our second long term goal: To establish an animal model system to ultimately identify biologically-active substances in aqueous humor.